Expression, subcellular localization and putative function of platelet‐type 12‐lipoxygenase in human prostate cancer cell lines of different metastatic potential

The involvement of 12‐lipoxygenase (12‐LOX) expression and function in tumor metastasis has been demonstrated in several murine tumor cell lines. In addition, 12‐LOX expression was detected in human prostatic tumors and correlated to the clinical stage of disease. Here we provide data that human prostate cancer cell lines express the platelet‐type isoform of 12‐LOX at both the mRNA and protein levels, and immunohistochemistry revealed 12‐LOX expression in human prostate tumors. The enzyme was localized to the plasma membrane, cytoplasmic organelles and nucleus in non‐metastatic cells (PC‐3 nm) and to the cytoskeleton and nucleus in metastatic cells (DU‐145). After orthotopic/intraprostatic injection of tumor cells into SCID mice, the metastatic prostate carcinoma cells (DU‐145) expressed 12‐LOX at a significantly higher level compared with the non‐metastatic counterparts, PC‐3nm. The functional involvement of 12‐LOX in the metastatic process was demonstrated when DU‐145 cells were pretreated in vitro with the 12‐LOX inhibitors N‐benzyl‐N‐hydroxy‐5‐phenylpentamide (BHPP) or baicalein, the use of which significantly inhibited lung colonization. These data suggest a potential involvement of 12‐LOX in the progression of human prostate cancer. Int. J. Cancer 87:37–43, 2000. © 2000 Wiley‐Liss, Inc.